Journal of Alzheimer's Disease - Volume 11, issue 1

Authors: Liu, Hsiu-Chih | Wang, Hsiao-Chien | Ko, Shun-Yao | Wang, Pei-Ning | Chi, Chin-Wen | Hong, Chen-Jee | Lin, Ker-Neng | Liu, Tsung-Yun

Article Type: Research Article

Abstract: This study analyzed whether platelet amyloid β-protein precursor (AβPP) isoform ratio correlates with cognition or cognitive decline in patients with Alzheimer's disease (AD). Platelet AβPP isoform ratio was measured, and cognitive assessment was performed using the Mini-Mental State Examination (MMSE) in 66 AD patients at baseline (T0) and in 29 of these patients in a one-year follow-up (T1). There was a significant correlation between the AβPP isoform ratios and MMSE scores in the 66 AD patients at T0. The T1 subjects were divided into two groups: 12 “no decliners” (MMSE score, T1–T0 ⩾ 0) and 17 “decliners” (MMSE score, T1–T0 …< 0). The decliners group showed a significantly greater reduction of AβPP isoform ratio from T0 to T1 than the no decliners group. However, the decline of the ratio did not correlate with the decline of MMSE score. These findings indicate that AβPP isoform ratio correlates with cognition, and reduction in this ratio may be a marker for cognitive decline in AD patients. Show more

Keywords: Alzheimer's disease, platelet, amyloid β-protein precursor (AβPP), AβPP isoform ratio, and Mini-Mental State Examination (MMSE)

DOI: 10.3233/JAD-2007-11111

Citation: Journal of Alzheimer's Disease, vol. 11, no. 1, pp. 77-84, 2007

Authors: Henriques, Ana Gabriela | Vieira, Sandra Isabel | Rebelo, Sandra | Domingues, Sara C.T.S. | da Cruz e Silva, Edgar F. | da Cruz e Silva, Odete A.B.

Article Type: Research Article

Abstract: Alzheimer's amyloid-β protein precursor (AβPP) can occur in different isoforms, among them AβPP751 , which is the most abundant isoform in non-neuronal tissues, and AβPP695 , often referred to as the neuronal isoform. However, few isoform-specific roles have been addressed. In the work here described, AβPP isoforms, both endogenous and as cDNA fusions with green fluorescent protein (GFP), were used to permit isoform-specific monitoring in terms of intracellular processing and targeting. Differences were particularly marked in the turnover rates of the immature isoforms, with AβPP751 having a faster turnover rate than AβPP695 (0.8 h and 1.2 h respectively …for endogenous proteins and 1.1 h and 2.3 h for transfected proteins). Hence, AβPP751 matures faster. Additionally, AβPP751 responded to both okadaic acid (OA) and phorbol 12-myristate 13-acetate (PMA), as determined by sAβPP production, with PMA inducing a more robust response. For the AβPP695 isoform, however, although PMA produced a strong response, OA failed to elicit such an induction in sAβPP production, implicating isoform specificity in phosphorylation regulated events. In conclusion, it seems that the AβPP695 isoform is processed/metabolized at a slower rate and responds differently to OA when compared to the AβPP751 isoform. The relevance of isoform-specific processing in relation to Alzheimer's disease needs to be further investigated, given the predominance of the AβPP695 isoform in neuronal tissues and isoform-specific alterations in expression levels associated with the pathology. Show more

Keywords: AβPP isoforms, okadaic acid, phorbol esters, AβPP targeting, phosphorylation

DOI: 10.3233/JAD-2007-11112

Citation: Journal of Alzheimer's Disease, vol. 11, no. 1, pp. 85-95, 2007

Authors: Jacob, C.P. | Koutsilieri, E. | Bartl, J. | Neuen-Jacob, E. | Arzberger, T. | Zander, N. | Ravid, R. | Roggendorf, W. | Riederer, P. | Grünblatt, E.

Article Type: Research Article

Abstract: Excitatory neurotransmitter dysfunction has been discussed to be involved in the pathophysiology of Alzheimer's disease (AD). In the current study we investigated gene and protein expression patterns of glutamatergic receptors and transporters in brains of AD patients in various stages of disease using gene chip arrays, real time PCR and immunohistochemistry. We found marked impairment in the expression of excitatory amino acid transporters (EAAT1 and EAAT 2) at both gene and protein levels in hippocampus and gyrus frontalis medialis of AD patients, already in early clinical stages of disease. The loss of EAAT immunoreactivity was particularly obvious in the vicinity …of amyloid plaques. In contrast, EAAT expression was up-regulated in the cerebellum of these patients. Furthermore, a significant up-regulation of the glutamatergic kainate (GRIK4) receptor observed by gene arrays was confirmed by quantitative RT-PCR in late stages in the hippocampus of AD patients. Moreover, there were down-regulations of other glutamatergic receptors such as NMDA (GRINL1A) and AMPA (GRIA4) receptors. Our data show marked changes in the functional elements of the glutamatergic synapses such as glutamatergic receptors and transporters and indicate impaired glutamate clearing rendering neurons susceptible to excess extracellular glutamate and support further the involvement of excitotoxic mechanisms in the pathogenesis of AD. Show more

Keywords: Alzheimer's disease, array, gene expression, glutamate, kainate, quantitative PCR

DOI: 10.3233/JAD-2007-11113

Citation: Journal of Alzheimer's Disease, vol. 11, no. 1, pp. 97-116, 2007

Authors: Santos, Alexander Navarrete | Torkler, Sandra | Nowak, Denny | Schlittig, Claudia | Goerdes, Mirjam | Lauber, Thomas | Trischmann, Lothar | Schaupp, Michael | Penz, Monika | Tiller, Friedrich-Wilhelm | Böhm, Gerald

Article Type: Research Article

Abstract: The neuropathology of Alzheimer's disease (AD) has been linked recently to non-fibrillar forms of neurotoxic amyloid-β (Aβ) oligomers of which high levels are observed in the brain of AD patients. This suggests that Aβ oligomers play a key role in the early events of AD, underlining their potential for the early diagnosis of the disease. We have developed an extremely sensitive assay for the detection of oligomeric and fibrillar structures of Aβ that is based on multiparametric analysis of data obtained by flow cytometry and fluorescence resonace energy transfer (Fret). The assay readily detects Aβ oligomers in human cerebrospinal fluid …(CSF) as verified by dot blot of the isolated particles. By measuring 174 CSF samples of non-demented control patients with various neurological disorders a high reliability and reproducibility of the method could be demonstrated. Show more

Keywords: Alzheimer's disease, amyloid-β oligomers, cerebrospinal fluid, flow cytometry, fluorescence resonance energy transfer

DOI: 10.3233/JAD-2007-11114

Citation: Journal of Alzheimer's Disease, vol. 11, no. 1, pp. 117-125, 2007

Authors: Strobel, Gabrielle

Article Type: Other

DOI: 10.3233/JAD-2007-11115

Citation: Journal of Alzheimer's Disease, vol. 11, no. 1, pp. 127-129, 2007

Authors: Strobel, Gabrielle

Article Type: Other

DOI: 10.3233/JAD-2007-11116

Citation: Journal of Alzheimer's Disease, vol. 11, no. 1, pp. 131-133, 2007

Article Type: Announcement

DOI: 10.3233/JAD-2007-11117

Citation: Journal of Alzheimer's Disease, vol. 11, no. 1, pp. 135-137, 2007

Article Type: Correction

DOI: 10.3233/JAD-2007-11118

Citation: Journal of Alzheimer's Disease, vol. 11, no. 1, pp. 139-139, 2007